Eyes of animals including humans play an important role in information transfer through the perception of peripheral information. That is, accurate images for a peripheral environment are continuously received through the eyes and information receiving the images is processed in the brain, and thus various functions inducing behaviors appropriate to the situation are performed. Like other organs in the body, a variety of diseases also occur in the eyes. The most common eye disease is keratitis, and includes glaucoma, cataracts and retinal disease. Particularly, scarring caused by corneal ulcer is a major cause of blindness and vision loss worldwide. This vision loss can be prevented by diagnosis of the cause and proper treatment (Vaughan General ophthalmology, 15/e professors of department of Ophthalmology, National Academy of Medicine). In addition, if the corneal ulcer is not treated rapidly but continued for a long time, a scar tissue is formed on the cornea, and new blood vessels enter the cornea, and as a result, transparency of the cornea is deteriorated and astigmatism may occur. Therefore, even after the corneal ulcer is treated, a persistent poor result in the vision may occur. Therefore, the treatment of corneal ulcer is an important therapeutic goal to treat the ulcer as soon as possible.
Alternatively, recently, for vision correction, a refractive corneal surgery using an excimer laser has been frequently performed. A method of cutting parenchymal cells of the cornea using an excimer laser is largely divided into lasik or lasek according to a method of peeling epithelial cells of the cornea. In the surgery, a scar tissue and the like that may remain very finely in the cornea after the vision correction surgery due to damage to corneal epithelial cells and damage to a part of the upper corneal parenchymal cells may affect postoperative pain and complications. Therefore, a rapid healing method of the corneal epithelial cells is a study field which is very importantly considered. In addition, in various ophthalmic procedures, protecting and rapidly regenerating the corneal epithelial cells may ultimately be an important part of effective eye treatment.
In current clinics or veterinary clinics, in order to promote recovery according to corneal injury caused by various factors, platelet rich plasma (PRP) and plasma protein-removed components have been developed and used, but it is not yet known which component plays the role. Glycerol- and sphingosine-based phospholipids are very abundant in the cell membrane and mainly structural components configuring the membrane. Further, these components are also present in the blood, and some components through metabolic processes form lysophospholipids (Okudaira et al., Biochimie 92, 698-706. 2010).
In the lysophospholipids, lysophosphatidylcholine (LPC) is included and receives an action of an enzyme of lysophospholipase D known as autotaxin to generate lysophosphatidic acid (LPA; 1- or 2-acyl-sn-glycerol-3-phosphate) (Aoki, Seminars Cell & Dev. Biol. 15, 477-489, 2004; Okudaira et al., Biochimie 92, 698-706. 2010). It is reported that in the early stage, the LPA is known to be produced when the platelets are activated and associated with hemostasis, wound healing, and tissue regeneration, but according to recent studies, it is known that the LPA is present in plasma, serum, saliva, seminal fluid, follicular fluid, and the like in addition to the platelets and is present at concentrations of 80 to 100 nM in the plasma and 1 to 5 M in the serum (Aoki, Seminars Cell & Dev. Biol. 15, 477-489, 2004). Further, it has also been found that the LPAs are widely distributed in a variety of cells such as adipocytes, fibroblasts, brain, and various organs (Pages et al., Prostaglandins 64, 1-10, 2001).
The LPA present in blood when binding primarily to plasma proteins (e.g., albumin) is more stable, and while the LPA is bound to the plasma proteins (mainly, albumin) and circulated with the plasma protein when the blood is circulated, the LPA is bound to a LPA receptor in a target organ to exhibit the effect (Croset et al., Biochem J 345, 61-67, 2000). A phosphate group and a glycerol backbone of the LPA play an important role in LPA action (Jalink et al., Biochem J. 307, 609-615, 1995). Although the LPA in which the phosphate group is present in the blood is present at 1 to 5 M, since the phosphate group of LPA is removed by an enzyme called lysophospholipid phosphatase in the blood or the cell membrane in a very short time and the LPA is inactivated, many studies on synthesis or development of LPA analogs which are not easily metabolized and works for a long time under the influence of enzymes have been conducted, but compounds suitable for clinical applications are not yet found (Pilquil et al., Prostaglandins. 64, 83-92, 2001; Brindley and Pilquil, J Lipid Res. 50 Suppl S225-230, 2009; Croset et al., Biochem J 345. 61-67, 2000; Deng et al., Gastroenterology 132. 1834-1851, 2007). It is expected that the protein component of gintonin serves to as stabilizer that protect and stabilize the LPAs.